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13 patients with adult non-lymphocytic leukemia (ANLL) who developed central nervous system (CNS) involvement during the course of their illness are reported and compared with a control group of 26 ANLL patients without CNS involvement. The incidence of CNS involvement was 13/510 patients (2.5%). Initial symptoms and signs and routine laboratory data were not helpful in predicting which patients would ultimately develop CNS involvement. Almost 1/2 of the patients were in clinical and haematological remission at the time of the diagnosis of CNS involvement. Specific treatment to the CNS including intrathecal cytotoxic drugs and/or radiotherapy failed to increase the survival rate significantly. Whether the establishment of an early diagnosis of CNS involvement and the institution of appropriate treatment may improve the prognosis of this complication is a question which presently remains unanswered.

Lymphocytes were obtained from a lymph node biopsy from a patient with chronic lymphocytic leukemia in whom B and T lymphocytes were present in equal percentages in the peripheral blood. The lymphocytes were examined for rosette formation with mouse and sheep erythrocytes in order to determine whether the leukemic process was of the B or T cell type.

Benign familial leukopenia was found in 75 of 200 healthy Yemenite Jews examined. The leukopenia was not a constant finding and was not associated with a tendency toward infection. HLA typing showed no significant differences in the frequency of the various HLA antigens between the subjects with and without leukopenia. No similarity was found between the HLA of the Yemenite Jews with leukopenia and that reported in black Africans with benign familial leukopenia. The suggestion of a genetic contribution from African blacks to Yemenite Jews is not supported by these results. The question remains to be answered whether the familial leukopenia in Yemenite Jews and black Africans is the result of a mutation.

Bacteremia during infection with Shigella is relatively rare and usually self-limited. Bacteremia during shigellosis bearing a high fatality rate has been reported in young infants and in persons with malnutrition or with the acquired immunodeficiency syndrome. We report a case of Shigella sonnei septicemia in a severely neutropenic patient who had fever, abdominal pain, diarrhea, malnutrition, and dehydration. She died after five days despite intensive care. We emphasize that Shigella should be considered among the possible pathogens causing sepsis in neutropenic patients.

The purpose of the present study was to document the increased leukocyte adhesiveness/aggregation (LAA) and tissue leukostasis that follow surgical trauma. We found that following major abdominal surgery, the percentage of aggregated leukocytes in the peripheral blood increased from 8.6 +/- 7 to 21.7 +/- 11.5 (p0.001), while the respective values for patients undergoing minor surgery were 3.7 +/- 2.4 and 19.7 +/- 7.6% (p0.001). The state of LAA was also determined in eight dogs after partial collectomy and four controls. A clear increment in the degree of tissue leukostasis (especially in the spleen, liver and lungs) was noted in the operated as compared to the control animals. In addition, a significant correlation was found between the state of LAA, determined in the venous (p = 0.0004) and arterial (p = 0.002) blood of these animals and the degree of tissue leukostasis. We conclude that a state of increased LAA in the peripheral blood is induced by surgical trauma and that this increased LAA correlates with tissue leukostasis.

Leukocyte endothelial interactions are essential for a normal immune response. It is known that this response is influenced by stress and that the latter induces demargination. We examined the question of whether stress demargination results from a decreased state of leukocyte adhesiveness. Included were various volunteers and patients under different degrees of stress. 66 young athletes before beginning their daily exercises, 67 middle-aged healthy volunteers, 25 patients before ergometry for evaluation of chest pain, 75 patients who were referred to the emergency room with chest pain without ischemia/infarction, 78 patients with ischemia/infarction, 65 patients with minor trauma, 25 with a fracture and 12 with polytrauma. The leukocyte adhesiveness/aggregation (LAA) values were measured with a direct slide test. The respective LAA values were 7.4 +/- 4.7, 6.3 +/- 4.4, 5.8 +/- 3.6, 5.2 +/- 3.5, 10.8 +/- 8.5, 9.1 +/- 5.8, 12.2 +/- 6.6 and 19 +/- 12.6% of aggregated leukocytes. We conclude that an increase in aggregated white blood cells can be detected in the circulating pool during major stress. It is therefore suggested that stress demargination is not necessarily a result of diminished leukocyte adhesiveness.

A patient with endocarditis caused by Corynebacterium CDC Group A-4 is described. This is the first case in the literature of endocarditis caused by this bacteria, and is unique in that the patient was immune competent and the infection occurred on a native valve. This case illustrates that corynebacteria cannot be considered a contaminant and that the exact pathogen should be identified.

Summary The association between the CREST (calcinosis, Raynaud phenomena, oesophageal hypomotility, sclerodactyly and telangiectasia, variant of systemic sclerosis and chronic lymphocytic leukaemia is described in three patients. The present description raises the possibility that the association of chronic lymphocytic leukaemia and systemic sclerosis is non-random.

The in vivo effects of three cytotoxic agents – cytosine arabinoside, daunomycin and hydroxyurea on rat bone marrow megakaryocytes were studied, specifically the relative count, the type percentage and the morphology. All three agents caused thrombocytopenia, a decrease in the number of megakaryocytes relative to the nucleated bone marrow cells, and a decrease in the percentage of megakaryoblasts, associated with an increase in the percentage of granular megakaryocytes. A decreased lobulation of the megakaryocytes was observed following the administration of cytosine arabinoside and of daunomycin. Thrombosthenin, examined immunologically, remained detectable in the bone marrow smears throughout the various stages of megakaryocyte alteration.

Cryoglobulinemia with peripheral cryoglobulinemic neuropathy is reported in a patient with Gaucher's disease. To the best of our knowledge, a similar relationship has not been previously described. The question whether the cryoglobulinemic neuropathy in this patient is related to Gaucher's disease, or is a mere coincidence, is discussed.

In order to assess the value of the leukergy test in which leukocytes aggregate in citrated whole blood, we examined 65 patients with various rheumatic conditions. In addition, plasma samples from 40 patients were examined for neutrophil aggregation activity in vitro. Results of the leukergy test were found to be in very good correlation with disease activity (P = 0.0001), whereas no increased neutrophil aggregation activity was found in the 40 plasma samples examined. The value of the leukergy test in assessing patients with rheumatic disease and its theoretical etiopathogenic role in these diseases are discussed.

After 3 years of treatment with azathioprine and prednisone, immunoblastic lymphoma appeared in a patient with systemic lupus erythematosus. An increased incidence of immunological aberrations and malignancies was found in her family and their relation to the pathogenesis of this patient's diseases is discussed.

A patient with chronic myelocytic leukemia in whom a clinical and hematological remission occurred after a single course of busulfan is described. The remission lasted for a period of 13 years and during that lapse of time, she gave birth to a healthy child. Afterwards, acute myeloblastic leukemia was diagnosed. Following treatment with rubidomycin and arabinoside C another remission was achieved, lasting already for 18 months.

Two out of 25 monoclonal anti-DNA autoantibodies that were produced by human-human hybridoma were found to have lymphocytotoxic activity. The antibodies reacted with normal B and T lymphocytes at cold (4 degrees C) as well as at warm (37 degrees C) temperatures. The lymphocytotoxic activity of the monoclonal anti-DNA antibodies could be inhibited by prior incubation of the antibodies with either polynucleotides, e.g. poly(I), poly(dT) or anti-idiotypic antibodies, that had been raised against a dominant anti-DNA antibody. The cross-reactivity between nuclear material and lymphocyte membrane raises the question whether these apparently diverse materials have a shared epitope. The cross-reactivity between anti-DNA antibodies and lymphocyte membrane may account in part for the lymphopenia observed in systemic lupus erythematosus patients.

A patient with multiple myeloma in whom recurrent right pleural effusion was the presenting sign of the disease is reported. An IgA (k) monoclonal component was found in both the pleural effusion and the serum. The bone marrow specimen was interpreted as typical for multiple myeloma and the pleural fluid contained numerous plasma cells. Treatment with cyclophosphamide was followed by clinical improvement and the disappearance of the pleural effusion.

Peripheral blood B and T lymphocytes were studied in 100 patients with polycythemia vera (PV), in whom no immunoglobulin abnormalities were detected. A significant decrease of the total lymphocyte count as well as of the relative and absolute values of B- and T-cell count was found. These results were unaffected by the modality of treatment, i.e., repeated phlebotomies or 32 P. However, in 28.8% of the PV patients a negative graft-versus-host reaction was found. This finding was significantly higher among the 32 P-treated PV patients (46.6%), when compared to the phlebotomy-treated ones (25.3%), suggesting possible reduced immuno competence in the 32 P-treated patients.

A patient with Hamman-Rich syndrome and palmo-plantar disarrangement of the epidermal ridges is reported. The significance of this association is discussed.

Monoclonal IgG components were found in the serum of 5 of 40 patients with chronic myelocytic leukemia (12.5%), as well as in 2 of 15 patients with acute myelocytic leukemia (13.3%). These findings may represent an involvement of the lymphoplasmacytic system in myeloproliferative disorders. The significance of this association is discussed.

The association between aggregates of leucocytes in blood drawn from patients with various inflammatory conditions and the serum concentration of C-reactive protein (CRP) was examined: serum concentration of CRP might contribute to the development of cellular aggregations. A total of 213 patients with various inflammatory or necrotic conditions were examined (including 31 women with normal pregnancy and 59 controls). A significant correlation between the degree of leucocyte aggregation and CRP concentration was noted in patients with bacterial infections and in a group of patients with various inflammatory conditions. In contrast, there was no correlation between the extent of leucocyte aggregation and CRP concentrations in patients with viral infections, malignancies, or pregnancy. The presence or absence of aggregated leucocytes can help in differentiating between the respective bacterial or viral infections. The serum concentrations of CRP were increased in both types of infection, although when a quantitative CRP assay was used, considerably higher concentrations were detected in bacterial diseases.

The coexistence of cryoglobulinemia and C4 deficiency was found in one family. Twelve subjects were examined, most of them being asymptomatic. Cryoglobulins were found in 9 members and its type was defined in 6 of them, 3 having mixed IgM-IgG and 3 having monoclonal IgM cryoglobulins. The concentration of the third component of the complement system was normal in 10 subjects, while the concentration of the fourth one was found to be below the lower limit of normal in 9 subjects. Only C4 deficiency--and not cryoglobulinemia--was HLA-linked. There was no evidence of HBs antigenemia. The results of this study are discussed in the light of the pertinent literature.

Seven of 60 human monoclonal anti-DNA autoantibodies derived from 3 patients with SLE were shown to bind to Raji cells by radioimmunoassay. The binding of the lupus autoantibodies to the Raji cells in solution was not affected by prior incubation of the cells with DNase. Preincubation of the monoclonal autoantibodies with polynucleotides and cardiolipin, resulted in significant inhibition which correlated with the direct binding characteristics of these antibodies. Previous results with mouse IgG monoclonal anti-DNA antibodies supported by our results with human IgM anti-DNA autoantibodies suggest caution in interpreting analyses of immune complexes of sera containing anti-DNA antibodies entailing Raji cells.

A heterozygous state for C4 deficiency was found in 14 members of a family with familial SLE. The HLA analysis in this family permitted us to re-establish the linkage assumed to exist between the gene (or genes) controlling the synthesis of the fourth component of the complement and the major histocompatibility complex. In addition, it was found that the complement deficiency is not necessarily associated with any serological or clinical abnormality. The heterozygous state for C4 deficiency can be added to the various serological abnormalities described in asymptomatic members of families with familial SLE. It is as yet unknown whether this deficiency may predispose to the subsequent development of SLE.

Six out of 8 healthy first-degree relatives of a patient with systemic lupus erythematosus (SLE) had very high serum levels of a common anti-DNA idiotype (16/6). In this family an additional sister developed SLE, and all members were heterozygous for C4 deficiency. Measurements of common autoantibody idiotypes may contribute to the understanding of the genetics of autoimmune diseases. They might be found useful in detecting healthy subjects prone to the development of an overt clinical state.

A markedly neutropenic patient with aplastic anemia who developed fever unresponsive to massive antibiotic treatment succumbed to mucormycosis pneumonia which could not be demonstrated by repeated che

A 16-year old patient with Fanconi's anemia developed pre-leukemia and pulmonary infiltration which was found upon autopsy to be pulmonary alveolar proteinosis. The question whether the pulmonary alveolar proteinosis was due to the marked leukopenia and an eventual defective phagocytic ability of the leukocytes is raised.

Generalized pruritus appeared 2 years following resection of an adenocarcinoma of the stomach. The appearance of the pruritus was the presenting symptom of recurrence of the malignant process in the stomach as well as of its metastatic spread to the liver and to the lungs.

Hemorrhagíc tendency and granulocytopenia due to prolonged contact with trichloroethylene and toluene are described in a boy whose hobby was model air-plane assembly. The hemostatic defects found were hypoproconvertinemia, moderate hypofibrinogenemia, and increased capillary fragility. The clinical and laboratory abnormalities disappeared following interruption of the exposure. The abnormalities in the coagulation mechanism are ascribed to a toxic effect of the trichloroethylene on the liver, while the granulocytopenia is considered to reflect a bone marrow-depressing action of benzene contaminating the toluene. The increased capillary fragility is presumed to be due to a toxic effect of the chemicals on the blood vessels.

A rapidly necrotizing leukemic skin infiltrate appeared simultaneously with a fatal blastic crisis in a patient with chronic erythroleukemia. Local X-ray irradiation and systemic cytotoxic, antibiotic and corticosteroid treatment were of no avail.

A patient with Gaucher's disease and non-secretory multiple myeloma is described. The presence of typical Gaucher and myeloma cells was confirmed by transmission and scanning electron microscopy. The immunological studies established the diagnosis of ‘non-secretory’ type of multiple myeloma.

Halothane, but not methoxyflurane, was found to cause specific hepatocellular damage, the hepatotoxicity being prompt but transient. The hepatotoxicity was demonstrated by the elevation in the serum activity of xanthine oxidase, a highly sensitive marker for acute liver damage.

To the Editor.— Serious side effects, including aseptic meningitis, were noted in several systemic lupus erythematosus (SLE) patients treated with ibuprofen (239:1062, 1978). 1-3 We presently describe a specific cell-mediated immunity (CMI) to ibuprofen in SLE. The study group consisted of 11 women with SLE—two treated with ibuprofen, while the others never received this agent. Sixteen patients with active rheumatoid arthritis (RA) (five of them treated with ibuprofen) as well as ten healthy persons served as control subjects. In seven of the 11 SLE patients, the disease was active at the time of examination, as evidenced by high titers of antinuclear factor, anti-DNA antibodies, and low titers of C3 and C4 complement components. All but one patient were treated with antiinflammatory drugs, including aspirin, indomethacin, phenylbutazone, or corticosteroids. In the SLE patients treated with ibuprofen, 800 to 1,200 mg/day, maculopapular skin rashes developed on the trunk and extremities. Fever occurred

Renal hypouricemia, that is hypouricemia due to a renal abnormality reflected in increased uric acid clearance, is a rare condition, either inborn or acquired. When genetically determined, it usually appears in association with other tubular defects, such as in the Fanconi (1) and Hartnup syndromes (2) and Wilson’s disease (3). Recently, we reported on a familial renal hypouricemia, associated with idiopathic hypercalciuria and decreased bone density (4). Renal hypouricemia due to an isolated renal tubular defect has been reported in a few subjects (5,6), but to our knowledge only once as a familial syndrome (7). We presently describe another family with renal hypouricemia, in whom the renal tubular defect relates to the handling of uric acid exclusively. The propositus, a 27-year-old Iraqian-born Jewish female, was followed at the Hematology Clinic since 1969, when a diagnosis of toxoplasmosis was established. All blood chemistry and hematological tests were normal, except for serum uric acid which ranged from 1.1 to 1.9 mg%. Urinary uric acid excretion on a regular diet ranged from 815–1008 mg/24 h, as determined colorimetrically (8). Serum ceruloplasmin level and urinary copper excretion were within the normal range.

Hypercalciuria is a relatively common etiological factor in calcium urolithiasis1. It may be one of the manifestations of various abnormalities, such as hyperparathyroidism, renal tubular acidosis, sarcoidosis and malignancy. However, in the majority of cases it is classified as idiopathic2. In a previous study3 of a large series of patients (50 males and 24 females) with idiopathic hypercalciuric urolithiasis (i.e. idiopathic hypercalciuria associated with urolithiasis) we found that 20% of the examined patients had a family history of renal stones. Only one of these patients had a large enough family to allow a detailed study which is reported in this paper.

Two patients in whom transient paralysis complicated cutaneous herpes zoster infection are described. The major features of this condition are reviewed.

The term idiopathic hypercalciuria (IH) refers to a syndrome of unestablished aetiology, comprising hypercalciuria, intestinal hyperabsorption of calcium, normocalcemia, normo- or hypophosphatemia, and a high frequency of calcium stones. Underlying primary mechanisms may include intestinal overabsorption, decreased tubular calcium reabsorption, and possibly increased bone catabolism.

Benign neutropenia is often found among healthy Yemenite Jews. An assessment was made of the magnitude of labor-induced leukocytosis in 44 Yemenite Jewish women, by comparing their hematological values during labor with those of 27 non-Yemenite women. A statistically significant difference was found in the absolute counts of the white blood cells (WBC) during delivery between the two groups, the values being lower among Yemenite Jews [10,291 +/- 422] vs. [11,759 +/- 630] X 10(9)/1) and similar findings were detected among their infants. The low WBC counts in the Yemenite group at parturition were also associated with significantly lower plasma cortisol levels (Yemenite group: 33.7 +/- 3.5 micrograms/dl; controls: 49.3 X 2.9 micrograms/dl). A correlation was found between serum cortisol levels and the magnitude of leukocytosis in both groups of women and their infants. These results suggest that a low basal corticosteroid output may contribute to the low white blood cell counts detected in some ethnic groups like the Yemenite Jews.

To the Editor.— Specific infiltrations in the mouth, while relatively frequent in the acute forms of leukemias, are rare in chronic lymphatic leukemia (CLL). 1,2 We presently report a CLL case in which a huge leukemic infiltration in the hard palate was diagnosed. Report of a Case.— A 77-year-old housewife, known to have CLL since 1972, was treated with chlorambucil and cyclophosphamide, monitored according to her blood counts. Her condition was satisfactory till June 1977, when she noted a painful swelling in her hard palate where a necrotic ulcer, 3×2 cm with regular and smooth border, was seen. A biopsy specimen from the latter showed massive infiltration with small lymphocytes, consistent with the diagnosis of CLL. A local cobalt irradiation (400 rads) completely healed this lesion. Comment.— Oral manifestations such as gingival hypertrophy, hemorrhages, ulcerations, necroses, and infections, while common in the acute forms of leukemia, are rare in CLL